This invention relates to apparatus and methods for treatment of ocular tissue and more particularly to altering opto-mechanical characteristics of targeted ocular tissue with the use of a continuous wave (CW) infrared laser in combination with other treatment modalities. This invention includes both the precise reshaping of corneal tissue for refractive correction and novel techniques for cross-linking the thermally treated corneal tissue to prevent such tissue from regressing to its original shape.
Overview of Current Cross-Linking Technology
Cross-linking is a widespread method used to harden polymer materials and to stabilize living tissue. More specifically in the medical arena, collagen cross-linking (CXL) and bonding technology has been used for many years in dentistry, orthopedics, and dermatology.
In 1998, a breakthrough occurred in ophthalmology when Theo Seiler, MD, PhD, of Zurich, Switzerland, used CXL to treat severe keratoconus (a progressive degenerative condition of the cornea where the tissue thins and bulges forward). By 2000, after significant research into the safety aspects of this procedure by Dr. Seiler, Gregor Wollensak, MD, and Eberhard Spoerl, PhD (Germany), CXL was adopted by surgeons worldwide outside of the U.S. (In the US, clinical trials for the current version of CXL are underway.) In 2007 CXL received regulatory approval as a procedure in the European Union.
The primary emphasis in the application of CXL for ophthalmology has been in the treatment of keratoconus, which is prevalent in about one in 2,000 people in the United States. This condition is manifested by a weak cornea that becomes too elastic and stretches, causing it to bulge outward. This condition changes the curvature of the cornea, which almost always leads to poor visual acuity (not correctable with glasses and/or soft contact lenses) that requires the use of rigid gas permeable lenses. Thus, when the cornea begins losing its shape (i.e., becomes cone shaped instead of spherical), nearsightedness (myopia) and irregular astigmatism result, which causes the blu'rring of vision. As this condition progresses, scarring and a very irregular corneal curvature may result. If a person cannot be helped with rigid contact lenses, then a corneal transplantation can be required.
There are other conditions/corneal diseases where the cornea can become stretched and distorted, for example, such as surgically induced astigmatism. Another of these, where CXL is currently being utilized for correction, is in corneal ectasia. This condition involves stretching of the cornea (a collagen tissue) that occurs after refractive surgeries, such as laser in situ keratomileusis (LASIK) or photo-refractive keratectomy (PRK). Other corneal diseases in which CXL treatment has been tried successfully include corneal ulceration (possible sequelae to bacterial, viral or fungal infections) and bullous keratopathy (excess fluid accumulation causing corneal edema).
The biomechanical basis of increased corneal strength (i.e., stability and stiffness) is the result of the formation of covalent cross-links that occur when the photosensitizer, riboflavin (Vitamin B-2), is applied to the de-epithelialized surface of the cornea. This excitation of the riboflavin by the UVA results in the creation of free radicals that interact with amino acids in neighboring collagen molecules to form strong chemical bonds.
Known CXL procedures are effective, but they are invasive and time-consuming, and they may have potential safety issues. In known procedures, 0.1% riboflavin is formulated with a polysaccharide made of many glucose molecules such as dextran, and then the surface layer of the cornea (epithelium) is surgically removed so the riboflavin can pass (i.e., be absorbed) into the stroma (collagen layers) of the cornea. The riboflavin is applied with an eye dropper manually every 3 to 5 minutes for a total of 30 minutes prior to treatment (the pre-soak procedure). Following the pre-soak a continuous UVA light (wavelength of approximately 365-370 nm) is projected on the cornea for approximately 30 minutes, and there is no mechanism for measuring the depth of irradiation. During UVA irradiation riboflavin is continuously applied manually every 3 to 5 minutes with an eye dropper.
Limitations of Existing CXL
In known procedures, there is no measurement as to how much riboflavin is in the stroma during the treatment, and there is no means to assure prevention of cell damage in the corneal endothelium, or in the limbus, which contains vital corneal limbal stem cells.
In short, the existing procedure employing CXL has been clinically proven (in Europe) to be safe. However, in its current form, the procedure is very crude and exhibits a number of significant limitations including but not limited to the following: the procedure takes too long (approximately one hour in total); removal of the corneal epithelium is required, making the procedure invasive and uncomfortable for the patient intra-operatively and for 3 to 4 days following surgery. These limitations clearly preclude the use of CXL for many corneal treatments that would require a fast and highly accurate process for stiffening and stabilizing the cornea.
Overview of Corneal Thermal Reshaping
It is known that thermal treatment of the cornea with various laser devices can reshape the cornea for refractive correction. Although some of the known thermal treatments have been FDA approved in the USA, all have eventually failed because of the natural regression of the cornea to its original shape. This regression may occur over time periods of months to a few years. Companies known to have been active in the field are Refractec (Conductive Kerotoplasty—CK), Thermal Vision, aka Avedro (Keraflex), Rodenstock (Diode Thermal Kerotoplasty—DTK withdrawn) and Sunrise (Laser Thermal Kerotoplasty—LTK withdrawn). However, there remains a need to predictably re-shape and stabilize the cornea after the thermal treatment, to increase the long-term success rate.
None of the aforementioned thermal treatments have been surface sparing, which means the outer layers of the cornea (epithelium and Bowman's membrane) may be damaged by these treatments. There are a number of negative outcomes that can occur from such damage: (1) there is pain and wound healing that can induce corneal haze and leave the cornea vulnerable to infection; (2) the structural integrity of the cornea is negatively impacted; (3) near-term predictability of refractive outcomes is poor. These negative outcomes can be alleviated by a thermal procedure which spares the epithelium and Bowman's membrane. The delivery of thermal radiation in a surface-sparing fashion has been performed in dermatology applications for surface treatment. These applications involve heat transfer that occurs as a result of passing thermal radiation through a cooled custom contact window on the skin, thereby protecting the epidermal layer.